Voriconazole

C difficile risk
Low
Oral Bioavailability
Excellent

Spectrum Of Activity

Dosing

  • IV: 6 mg/kg IV q12h x 2 doses then 4 mg/kg IV q12h

  • PO : 400 mg PO q12h x 2 doses then 200 mg PO q12h

Dose reduction may be required if low body weight.

0 - 50 eGFR50+ eGFRIV formulation not recommended due to accumulation of vehicle (cyclodextrin), switch to oral. No dose modification needed.No dose adjustment required.

Severe impairment (Child-Pugh C) - Should only be used if benefit outweighs risk

Mild to moderate (Child-Pugh A/B) - Standard loading dose then reduce maintenance by 50%

General Information

Candida infections both mucocutaneous and invasive - i.e. Candidemia

Antifungal prophylaxis in immunocompromised

Pregnancy:

  • Single case report in human pregnancy (after 19 wga), normal healthy baby

  • Animal data suggest teratogenicity

  • Caution due to data from fluconazole (see fluconazole entry)

Breastfeeding:

  • No data. References conflicting on recommendations. While limited, therapeutic dosing available for neonates and infants for invasive fungal infections.

Therapeutic drug monitoring may be helpful to ensure adequate concentrations and exclude toxicity

QTc interval in patients at elevated risk

Monitor hepatic profile

Creatinine, electrolytes (K+, Mag+, Ca+)

  • QTc prolongation

  • Hepatotoxicity, renal toxicity

  • Rash; dermatologic reactions

  • Visual disturbance, photophobia, headache, dizziness,

  • Fluorosis

  • Hypokalemia, hypomagnesemia

  • Multiple significant drug interactions, consult pharmacy.

  • CYP450 interactions ++

  • Other QTc prolonging agents

  • Contraindicated with pimozide, quiniDINE, rifampin, carbamazepine, sirolimus, rifabutin, ritonavir, efavirenz, ergot alkaloids, and phenobarbital

  • Voriconazole may inhibit the metabolism of tacrolimus (need to decrease tacrolimus dose to 1/3 of original dose), cycloSPORINE (need to decrease cycloSPORINE dose by 50%), sulphonylureas, statins, and HIV protease inhibitors other than indinavir

  • Voriconazole increases concentration of phenytoin. Phenytoin decreases concentration of voriconazole. Drug monitoring recommended.

  • Recommend review of patient medications due to high frequency of significant interactions

Food may decrease oral absorption. Should be taken 1hr before or 1 hr after a meal

Avoid/limit use of IV formulation in renal failure due to accumulation of vehicle (cyclodextrin)

Infectious Disease consult strongly recommended.

Antimicrobial class: Triazole antifungal, second generation.